The field of the invention is systems and methods for magnetic resonance imaging (“MRI”). More particularly, the invention relates to systems and methods for separating signal contributions from two or more chemical species using MRI.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the western world, affecting an estimated 100 million Americans. NAFLD is associated with obesity, diabetes, and the metabolic syndrome, and is rapidly becoming a leading cause of liver failure and hepatocellular carcinoma. It is currently the second leading indication for liver transplantation at University of Wisconsin-Madison, and is expected to overtake viral hepatitis as the leading cause, within the next decade. Given the increasing worldwide epidemic of obesity and diabetes, it is expected that this disorder will grow in prevalence.
The earliest and hallmark feature of NAFLD is the abnormal accumulation of intracellular triglycerides within hepatocytes. Accumulation of fat within hepatocytes can lead to hepatocyte injury and inflammation, and subsequent development of fibrosis and cirrhosis, and eventually carcinoma and/or liver failure. The presence of inflammation and liver fibrosis, known as nonalcoholic steatohepatitis (NASH) is a more aggressive subset of NAFLD. Identification of those patients with NASH is a key diagnostic consideration. Biopsy is the currently accepted reference standard for the diagnosis, grading, and staging of NAFLD/NASH. However, biopsy is expensive, invasive, and is limited for quantitative grading and staging due to the inherent sampling variability from sampling a small amount of tissue within the liver.
Some have tried to develop non-invasive techniques for even just diagnosis of NAFLD/NASH. Such techniques would reduce the need for invasive biopsy until a diagnosis for NAFLD/NASH, whereby the biopsy is performed for grading and staging. Of course, it would be preferred to have a non-invasive technique that enables diagnosis, grading, and staging of NAFLD/NASH.
Emerging, quantitative magnetic resonance imaging-based biomarkers have shown promise in recent years for quantifying features of diffuse liver disease, including fat content, R2*(=1/T2*) as a biomarker of iron concentration. Also, other biomarkers, such as provided by techniques like MR elastography, can provide measures of tissue stiffness as a biomarker of liver fibrosis.
More recently, some have proposed a T1 mapping technique to serve as a biomarker of extracellular fluid (ECF) content and fibrosis. For example, this technique is described in US Patent Publication No. 2014/0330106. In particular, in the presence of fibrosis, the water content of tissue will increase, which lengthens tissue T1. However, in the presence of diffuse liver disease, iron often accumulates. Iron, in addition to shortening T2*(increasing R2*), shortens T1. Thus, such methods relying on T1 mapping can be confounded by the shortened T1 caused by the presence of iron.
Some have sought to address this challenge, in part, by acquiring a second dataset that is used to correct the first dataset that is acquired to create the T1 map. In this way, two data sets are acquired to create a “corrected” T1 map. Specifically, a first MRI data acquisition is performed to acquire a T1 map using a “modified Look-Locker” or MOLLI approach. Then, a second MRI acquisition is performed to acquire a T2*map. For a given pixel in the T1 map, the corresponding T2*value is used to make an empirical correction for T1. In this way, an iron-corrected estimate of T1 is provided.
This approach has the undesired requirement that two separate datasets must be acquired. First, the need to acquire two datasets increases scan time. Second, the use of two separately-acquired datasets creates the prospect of mis-registration between the T1 and T2*maps.
Thus, it would be desirable to have non-invasive tools for evaluating, including diagnosis, grading, and staging, organs, including the liver.